Causal effects of serum testosterone levels on brain volume: a sex-stratified Mendelian randomization study.

PURPOSE: To assess the causal effects of serum testosterone and sex hormone-binding globulin levels on brain volumetric measurements in women and men. METHODS: We performed a sex-stratified two-sample Mendelian randomization study using the random-effects inverse variance-weighted method as the primary analysis method. Sex-specific genetic instruments were obtained from a study with up to 194,453 men and 230,454 women. For testosterone, variants with dominant effects on both total and bioavailable testosterone but no aggregate effect on sex hormone-binding globulin were used as the main genetic instruments. Sex-specific summary-level data for magnetic resonance imaging brain volumetric measurements were obtained from a study with 11,624 women and 10,514 men. RESULTS: Analyses showed per standard deviation (approximately 3.7 nmol/L) higher testosterone levels in men were suggestively associated with larger gray matter volume (beta = 0.208, 95% confidence interval = 0.067 to 0.349, p = 0.004). The association remained in sensitivity analyses and multivariable analyses. Further analyses showed the effect was mainly act on peripheral cortical gray matter, but not on subcortical gray matter. Testosterone in men was not associated with hippocampal volume. Testosterone in women and sex hormone binding globulin in both sexes had no effect on all outcomes. CONCLUSION: Our findings overall support previous evidence that testosterone might have neuroprotective properties in elderly men. Future larger trials with long duration of intervention are warranted to assess the efficacy of testosterone for elderly men with cognitive impairment, especially in those with hypoandrogenism.

Relationship between endothelial nitric oxide synthase gene polymorphisms and ischemic stroke: a meta-analysis.

OBJECTIVES: Previous studies examining whether polymorphisms (G894T, 4b/a, and T786C) in the endothelial nitric oxide synthase (eNOS) gene are associated with ischemic stroke have yielded conflicting results. We performed a meta-analysis to investigate the potential association between these three eNOS gene polymorphisms and ischemic stroke risk. MATERIALS AND METHODS: We searched databases until April 30, 2012 and used fixed or random effects models to estimate the pooled odds ratios (ORs). RESULTS: We analyzed 34 case-control data sets from 33 publications involving 5261/5823 cases/controls for G894T, 4295/4682 for 4b/a, and 2698/3254 for T786C polymorphisms. For Asian populations, all models showed significantly increased risk of ischemic stroke for the G894T (dominant model: OR = 1.58; 95% CI, 1.30-1.91; P = 0.000) and 4b/a polymorphisms (dominant model: OR = 1.46; 95% CI, 1.25-1.71; P = 0.000), even after Bonferroni correction (because 0.000 < 0.017). In white populations, the aa genotype seemed to be protective for ischemic stroke, as indicated by the recessive model (OR = 0.44; 95% CI, 0.22-0.87; P = 0.019). In Asian populations, the T786C polymorphism was significantly associated with ischemic stroke, as found using the dominant (OR = 1.17; 95% CI, 1.02-1.34; P = 0.025) and additive models (OR = 1.18; 95% CI, 1.05-1.33; P = 0.006). CONCLUSIONS: Our comprehensive meta-analysis ascertains that the G894T, 4b/a, and T786C polymorphisms are associated with ischemic stroke risk in Asians. A possible contrasting role of the 4b/a polymorphism in ischemic stroke was indicated in white populations.

Effects of Dietary Chromium Methionine on Growth Performance, Carcass Composition, Meat Colour and Expression of the Colour-related Gene Myoglobin of Growing-finishing Pigs.

To investigate the effect of dietary chromium (Cr) as Cr methionine (CrMet) on growth performance, carcass traits, pork quality, meat colour and expression of meat colour-related genes in growing-finishing pigs, 189 crossbred Duroc×(Landrace×Yorkshire) growing-finishing pigs (male, castrated, average initial BW 74.58±1.52 kg) were selected and randomly allocated into four groups. Dietary treatments per kg of feed were as follows: 0 (CT), 0.3 mg/kg (T1), 0.6 mg/kg (T2) and 0.9 mg/kg (T3) Cr (in the form of CrMet; as-fed basis), and each treatment was replicated five times with 8 to 10 pigs per replicate pen. During the 28 d of the experiment, both the ADG and the ADFI increased linearly (p<0.05) as the level of dietary Cr increased. The F/G ratio decreased linearly (p<0.05). As dietary Cr increased, loin muscle areas (linear, p = 0.013) and average backfat thickness (linear, p = 0.072) decreased. Shear force (linear, p = 0.070) and Commission Internationale de I'Éclairage (CIE) redness (quadratic, p = 0.028) were increased. In addition, CIE Lightness (quadratic, p = 0.053) were decreased as dietary Cr increased. As dietary Cr increased, total myglobin (Mb) content (quadratic, p = 0.015) and the mb mRNA levels (quadratic, p = 0.046) in longissimus muscles of pigs were up-regulated. In conclusion, supplementation of dietary Cr improved growth and meat colour, but increased shear force and decreased IMF reduced palatability of longissimus muscles. Moreover, the increasing total Mb content and mb mRNA levels indicated that CrMet dietary supplementation may improve meat colour via up-regulating expression of the mb gene.

Genome-wide association study reveals a quantitative trait locus and two candidate genes on Sus scrofa chromosome 5 affecting intramuscular fat content in Suhuai pigs.

Intramuscular fat content (IFC) is an essential quantitative trait of meat, affecting multiple meat quality indicators. A certain amount of IFC could not only improve the sensory score of pork but also increase the flavour, tenderness, juiciness and shelf-life. To dissect the genetic determinants of IFC, two methods, including genome-wide efficient mixed-model analysis (GEMMA) and linkage disequilibrium adjusted kinships (LDAKs), were used to carry out genome-wide association studies for IFC in Suhuai pig population. A total of 14 and 18 significant single nucleotide polymorphisms (SNPs) were identified by GEMMA and LDAK, respectively. The results of these two methods were highly consistent and all 14 significant SNPs in GEMMA were detected by LDAK. Seven of the 18 SNPs reached the genome-wide significance level (P < 9.85E-07) while 11 cases reached the suggestive significance level (P < 1.77E-05). These significant SNPs were mainly distributed on Sus scrofa chromosome (SSC) 5, 3, and 7. Moreover, one locus resides in a 2.27 Mb (71.37-73.64 Mb) region on SSC5 harbouring 13 significant SNPs associated with IFC, and the lead SNP (rs81302978) also locates in this region. Linkage disequilibrium (LD) analysis showed that there were four pairs of complete LD (r2 = 1) among these 13 SNPs, and the remaining 9 SNPs with incomplete LD (r2 ≠ 1) were selected for subsequent analyses of IFC. Association analyses showed that 7 out of 9 SNPs were significantly associated with IFC (P < 0.05) in 330 Suhuai pigs, and the other 2 SNPs tended to reach a significant association level with IFC (P < 0.1). The phenotypic variance explained (PVE) range of these 9 SNPs was 0.92-3.55%. Meanwhile, the lead SNP was also significantly associated (rs81302978) with IFC (P < 0.05) in 378 commercial hybrid pigs (Pietrain × Duroc) × (Landrace × Yorkshire) (PDLY), and the PVE was 1.38%. Besides, two lipid metabolism-relevant candidate genes, the leucine rich repeat kinase 2 (LRRK2) and PDZ domain containing ring finger 4 (PDZRN4) were identified in the 2.27 Mb region on SSC5. In conclusion, our results may provide a set of markers useful for genetic improvement of IFC in pigs and will advance the genome selection process of IFC on pig breeding programmes.

Association between Serum Uric Acid Level and Carotid Atherosclerosis in Chinese Individuals Aged 75 Years or Older: A Hospital-Based Case-Control Study.

OBJECTIVES: To investigate the association between serum uric acid level and the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older. DESIGN: Case-control study. SETTING: In a teaching hospital. PARTICIPANTS: Five hundred and sixty-four elderlies (75 years or above) who underwent general health screening in our hospital were enrolled. MEASUREMENTS: The detailed carotid ultrasound results, physical examination information, medical history, and laboratory test results including serum uric acid level were recorded, these data were used to analyze the relationship between serum uric acid level and carotid atherosclerosis. Then, subjects who underwent the second carotid ultrasound 1.5-2 years later were further identified to analyzed the relationship between serum uric acid and the progression of carotid atherosclerosis. RESULTS: A total of 564 subjects were included, carotid plaque was found in 482 (85.5%) individuals. Logistic regression showed that subjects with elevated serum uric acid (expressed per 1 standard deviation change) had significantly higher incidence of carotid plaque (odds ratio, 1.37; 95% confidence interval, 1.07-1.75; P= 0.012) after controlling for other factors. A total of 236 subjects underwent the follow-up carotid ultrasound. Linear regression showed that serum uric acid level (expressed per 1 standard deviation change; 1 standard deviation = 95.5 µmol/L) was significantly associated with percentage of change of plaque score (P = 0.008). Multivariable linear regression showed that 1 standard deviation increase in serum uric acid levels was expected to increase 0.448% of plaque score (P = 0.023). CONCLUSION: The elevated serum uric acid level may be independently and significantly associated with the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older.